DESCRIPTION (Applicant's abstract): Over the past decade, intravenous drug users (IDUs) have surprised policy makers and researchers by exhibiting large-scale HIV risk reduction, despite the fact that the majority of drug injectors axe unwilling or unable to enter formal drug treatment. Needle exchange programs offer direct contact with drug users who have initiated HIV risk reduction. The maintenance of risk reduction among out-of-treatment IDUs has never been studied. In the present study we suggest that the presence of depression among needle exchangers who have gone at least six months without sharing injection equipment places them at risk for a return to unsafe drug injection behaviors. Using a randomized, controlled design, enrolling 265 needle exchange clients in Providence, Rhode Island, this study provides the opportunity to treat the patient's depressive symptoms and thereby further sustain HIV risk reduction. The Primary Aim of the present application is: To test if treatment for depression using antidepressant medication will maintain safe injection behaviors among needle exchange clients compared to a treatment-as-usual condition. The Secondary Aim is: To determine if antidepressant medication treatment will reduce depressive symptom scores compared to the treatment-as-usual condition. The Tertiary Aims are: 1) To determine if reduction in depressive symptoms is associated with maintenance of safe injection behaviors, and 2) To describe specific patient characteristics associated with maintenance of safe injection behaviors. Given that many injection drug users (IDUs) continue to inject drugs over decades, maintaining HIV risk reduction is a critical public health problem. Our results will have policy implications for needle exchange programs where many IDUs have initiated HIV risk reduction.